Frictional tissue sampling and collection method and device

ABSTRACT

In an embodiment of the invention, a frictional tissue sampling device with a head designed to be rotated without rotating off the designated site can be used to obtain tissue biopsy samples. A frictional tissue sampling device with a head designed to be rotated without rotating off the designated site can be used to obtain an epithelial tissue biopsy sample from lesions. The device can be otherwise used to sample specific locations. In various embodiments, the head of the device is narrow and pointed with a hybrid pear shaped diamond facet. The facet contour can be concave, convex or flat. Abrasive material can be adhered to the facet contour.

PRIORITY CLAIM

This application is a divisional of and claims priority to (1) U.S.Utility Pat. No. 9,044,213, entitled “FRICTIONAL TISSUE SAMPLING ANDCOLLECTION METHOD AND DEVICE” by Neal M. Lonky filed Mar. 28, 2011 whichissued Jun. 2, 2015, which claims priority to (2) U.S. ProvisionalApplication No. 61/318,128, entitled “FRICTIONAL TISSUE SAMPLING ANDCOLLECTION METHOD AND DEVICE” by Neal M. Lonky filed Mar. 26, 2010,which applications (1)-(2) are herein expressly incorporated byreference in their entireties.

CROSS REFERENCE TO RELATED APPLICATION

This application is related to the following applications: (1) U.S.Utility patent application Ser. No: 12/669,638, entitled “FRICTIONALTRANS-EPITHELIAL TISSUE DISRUPTION AND COLLECTION APPARATUS AND METHODOF INDUCING AND/OR AUGMENTING AN IMMUNE RESPONSE” by Neal M. Lonky etal., filed Jan. 19, 2010, and (2) U.S. Utility patent application Ser.No: 13/072,773, entitled “FRICTIONAL TRANS-EPITHELIAL TISSUE DISRUPTIONCOLLECTION APPARATUS AND METHOD OF INDUCING AN IMMUNE RESPONSE” by NealM. Lonky et al., filed on the same date as this application. Theseapplications (1)-(2) are herein expressly incorporated by reference intheir entireties.

FIELD OF THE INVENTION

This invention relates to a method of and device for obtaining a biopsytissue sample.

BACKGROUND OF THE INVENTION

A lesion is caused by any process that alters or damages tissue. Alesion can be defined as any pathological or traumatic discontinuity oftissue with partial loss of tissue function. The concept of a lesionincludes wounds, sores, ulcers, tumors, cataracts and any other tissuedamage. Lesions can range from the skin sores associated with eczema tothe changes in lung tissue that occur in tuberculosis. Generally, alesion can be characterized by the epithelium covering the connectivetissue becoming fragile, leading to ulceration and bleeding.

Human papillomaviruses (HPV) are responsible for many cutaneous andmucosal lesions. Some viral genotypes are considered to be the causalagents of cervical cancer. Natural genital HPV infection seems to bepoorly immunogenic because of its nonproductive and non-inflammatorycharacteristics and also because of mechanisms developed by the virus tocounteract the immune response. Cervicovaginitis refers to inflammationof the squamous epithelium of the vagina and cervix caused by aninflammatory reaction to an infection. This damage leads to desquamationand ulceration, which can cause a reduction in the epithelial thicknessdue to loss of superficial and part of the intermediate layers of cells.In the deeper layers, the cells are swollen with infiltration ofneutrophils in the intercellular space. The surface of the epithelium iscovered by cellular debris and inflammatory mucopurulent secretions. Theunderlying connective tissue is congested with dilatation of thesuperficial vessels and with enlarged and dilated stromal papillae. Rareand uncommon cervical infections, due to tuberculosis, schistosomiasisand amoebiasis, cause extensive ulceration and necrosis of the cervixwith symptoms and signs mimicking invasive cancer. Herpes simplex virus(HSV) can be present on the mucosal lining of the mouth or genitals. Alarge coalesced ulcer due to HSV can also mimic the appearance ofinvasive cancer. Chronic inflammation causing recurrent ulceration andhealing of the cervix can result in a distortion of the cervix.Infections with the pathogenic fungi Cryptococcus neoformans,Histoplasma capsulatum, and Coccidioides immitis can be disseminated andsome, e.g., C. neoformans, can result in pneumonia or meningitis.Longstanding viral, bacterial, fungal or protozoal infection andinflammation may lead to white or pink appearance as a result offibrosis.

Previous devices to obtain a biopsy sample include brushes with rigidbristles that puncture and shear epithelial surfaces (U.S. Pat. No.5,535,756 “Catheter with simultaneous brush cytology and scrape biopsycapability”, U.S. Pat. No. 6,258,044 “Apparatus and method for obtainingtransepithelial specimen of a body surface using a non-laceratingtechnique”, U.S. Pat. No. 6,494,845 “Retractable brush for use withendoscope for brush biopsy” and U.S. Pat. No. 6,132,421 “Integratedepithelial removal tool”), single metal or plastic curettes that extendin a parallel direction to the applicator handle and are much largerthan the innovation (U.S. Pat. No. 4,641,662 “Endocervical curettesystem” and U.S. Pat. No. 6,730,085 “Surgical biopsy instrument”),scalpels or similar bladed sharp cutting tools (U.S. Pat. No. 5,857,982“Apparatus and method for removing tissue”, U.S. Pat. No. 5,800,362“Cervical biopsy device”, U.S. Pat. No. 3,774,590 “Uterine SpecimenCollecting Method”, U.S. Pat. No. 5,092,345 “Uterine cell sampler”,U.S.Pat. No. 4,061,146 “Tissue macerating instrument”, U.S. Pat. No.5,868,668 “Surgical instrument”, U.S. Pat. No. 6,053,877 “Movable sampletube multiple biopsy sampling device”, U.S. Pat. No. 5,470,308 “Medicalprobe with biopsy stylet”, U.S. Pat. No. 7,137,956 “Endoscopicsubmucosal core biopsy device”, U.S. Pat. No. 4,168,698 “Endocervicalstrip biopsy instrument” and U.S. Pat. No. 4,757,826 “Endocervicalbiopsy instrument”; and U.S. Publication No. 2005/0059905 “Tissueextraction and maceration device” and U.S. Pat. No. 2007/0093727“Cervical tissue biopsy system and methods of use”), or very largeelectrified metal loops used to produce excisional biopsies (U.S. Pat.No. 5,913,857 “Methods and devices for collection of soft tissue” andU.S. Pat. No. 5,951,550 “Endocervical conization electrode apparatus”).One device performs simultaneous brush cytology and scrape biopsy onstructures with an organic duct (U.S. Pat. No. 5,535,756, “Catheter withsimultaneous brush cytology and scrape biopsy capability”). U.S. Pat.No. 5,643,307 “Colposcopic Biopsy Punch with Removable Multiple SampleBasket” has also been proposed to obtain biopsy samples when examiningthe cervix.

SUMMARY OF THE INVENTION

There is significant incentive for being able to obtain a biopsy sampleof cells from a lesion in a manner which involves minimal pain and inthe least intrusive manner. In an embodiment of the present invention,an apparatus for obtaining a biopsy sample includes a handle, a flat,concave or convex surface at a distal end of the handle, and a fabricfor functionally abrading tissue surfaces applied to the surface. In anembodiment of the present invention, an apparatus for obtaining ahistological sample includes a handle, a flat, concave or convex facetsurface on the head at a distal end of the handle, and a fabric forfunctionally abrading epithelial surfaces. In an alternative embodimentof the present invention, an apparatus for obtaining a histologicalsample includes a handle, a flat, concave or convex facet surface on thehead at a distal end of the handle, and a fabric for functionallyabrading epithelial surfaces including a backing material and aplurality of fenestrated loops attached to the backing material. Aconcave facet surface with an adherent abrasive fabric allows the handleto be rotated and remain on the desired location to collect a biopsyfrom convex tissue surfaces. A convex facet surface with an adheredabrasive fabric allows the hand to be rotated and remain on the desiredlocation to collect a biopsy from concave tissue surfaces. A flat facetsurface with an adherent abrasive fabric allows the hand to be rotatedand pressed completley without allowing gaps between the abrasionmaterial and a flat surface tissue to be sampled when collecting abiopsy.

In an embodiment of the present invention, the device and the fabric aremade of materials that allow the fabric to be ultrasonically welded tothe device. In an alternative embodiment of the present invention, thefabric is attached to the device using an adhesive. In variousembodiments of the present invention, an ultra violet (UV) lightactivated adhesive can be used to affix the fabric to the device. Arailing or dam can be introduced onto the facet of the head of thedevice and the UV light activated adhesive is placed within the confinesof the dam made on the facet by the railing.

BRIEF DESCRIPTION OF THE DRAWINGS

This invention is described with respect to specific embodimentsthereof. Additional features can be appreciated from the Figures inwhich:

FIG. 1 is an apparatus for frictional trans-epithelial tissue disruptionof an epithelial flat surface;

FIG. 2(A) is a side view of an apparatus for frictional trans-epithelialtissue disruption of an epithelial lined canal surface with tapered conetip, FIG. 2(B) is an oblique view of an apparatus for frictionaltrans-epithelial tissue disruption of an epithelial lined canal surfacewith tapered cone tip, FIG. 2(C) is a top view of an apparatus forfrictional trans-epithelial tissue disruption of an epithelial linedcanal surface with tapered cone tip;

FIG. 3(A) is a schematic diagram showing a method of frictionaltrans-epithelial tissue disruption of a flat epithelial surface, FIG.3(B) is a schematic diagram showing a method of frictionaltrans-epithelial tissue disruption of an epithelial surface of a canalor body cavity;

FIG. 4 is a frictional trans-epithelial tissue disrupter with amotorized or vibratory handle used to spin or agitate the fenestratedloops;

FIG. 5 is a schematic diagram of an apparatus with a detachable platformthat anchors fiber loops at a distal end of the handle;

FIG. 6(A) is a schematic diagram of frictional trans-epithelial tissuedisruption showing a representation of tissue with a squamous epitheliallined surface, FIG. 6(B) is a schematic diagram of frictionaltrans-epithelial tissue disruption showing an application of thefrictional biopsy device to the body surface, FIG. 6(C) is a schematicdiagram of frictional trans-epithelial tissue disruption showingsimultaneous pressure, agitational, and rotational force splays andseparates the hooks/loops. Frictional abrasive forces create heat whichbuckles the epithelial surface, FIG. 6(D) is a schematic diagram offrictional trans-epithelial tissue disruption showing sufficientabrasion creates shearing and fracture of the epithelial surface atvarying depths which can include fracture through the basement membraneinto the subcutaneous layer, FIG. 6(E) The is a schematic diagram offrictional trans-epithelial tissue disruption showing the hooksinsinuate into the fracture plane, and with additional abrasive forcescontinue to shear the tissue fragments, while simultaneously retainingthe tissue for capture and collection, FIG. 6(F) is a schematic diagramof frictional trans-epithelial tissue disruption showing at thecompletion of the biopsy process, the collection of hooks arranged inrows create channels which collect and sequester the tissue and cellcluster fragments within the channels created in the device. When thedevice is removed from the epithelial surface, additional sample iscaptured and held due to the flexibility and recoil of the hooks;

FIG. 7(A) is a side view of a focal biopsy apparatus, depicted at theouter lip of the cervix (exocervix);

FIG. 7(B) is a schematic diagram of an apparatus for focal biopsies withan enlarged view of the platform and loops;

FIG. 8(A) is a side view of an apparatus for simultaneous biopsy ofepithelial surfaces and canal-like surfaces. Longer central core fibersto insinuate into a canal and a perimeter of approximately 3 mm fiberscontact an outer epithelial surface;

FIG. 8(B) is a schematic diagram of an apparatus for simultaneous biopsyof epithelial surfaces and canal-like surfaces with enlarged view ofplatform and loops;

FIGS. 9(A) and (B) are flowcharts showing the use of the FrictionalTissue Sampling and Collection (FTSC) device used to take anendo-cervical biopsy sample in accordance with an embodiment of theinvention;

FIG. 10 is a schematic side view of an exo-cervical FTSC device inaccordance with an embodiment of the invention;

FIG. 11(A) is a schematic side view of an endo-cervical FTSC device inaccordance with an embodiment of the invention;

FIG. 11(B) is an expanded side view of an endo-cervical FTSC head with asingle diamond shaped facet in accordance with an embodiment of theinvention;

FIG. 12(A) is a schematic side view of an exo-cervical FTSC device inaccordance with an embodiment of the invention;

FIG. 12(B) is a schematic front view of an exo-cervical FTSC inaccordance with an embodiment of the invention;

FIG. 12(C) is a schematic side view of an endo-cervical FTSC deviceshowing a single facet in accordance with an embodiment of theinvention;

FIG. 12(D) is a schematic front view of an endo-cervical FTSC deviceshowing a hybrid diamond-pear shaped facet in accordance with anembodiment of the invention;

FIG. 13(A) is a side view of an FTSC device with a cylinder extendingfrom the distal surface of a disc and the disc connected to the handleand the collection material attached on the distal surface of thecylinder in accordance with an embodiment of the invention;

FIG. 13(B) is a side view of an FTSC device with a cylinder extendingfrom the distal surface of a disc and the disc connected to a handle inaccordance with an embodiment of the invention;

FIG. 13(C) is an expanded side view of an FTSC device with a cylinderextending from the distal surface of a disc as shown in FIG. 13(B) andthe collection material attached on the distal surface of the disc andcollection material attached to the distal surface of the cylinder inaccordance with an embodiment of the invention;

FIG. 13(D) is a side view of an FTSC device with an elongated cylinderextending from the distal surface of a disc in accordance with anembodiment of the invention and the disc connected to a handle;

FIG. 13(E) is an expanded side view of an FTSC device with an elongatedcylinder extending from the distal surface of a disc as shown in FIG.13(D) and the collection material attached on the distal surface of thedisc and the surface of the cylinder in accordance with an embodiment ofthe invention;

FIG. 13(F) is a side view of an FTSC device with a cylindrical facetextending from the distal surface of a disc and the disc connected to ahandle in accordance with an embodiment of the invention;

FIG. 13(G) is a side view of an FTSC device with an elongated cylinderwith a rounded tip extending from the distal surface of a disc inaccordance with an embodiment of the invention and the disc connected toa handle;

FIG. 13(H) is a side view of an FTSC device with a cylindrical facetextending from the distal surface of a cone shaped disc and the discconnected to a handle and the collection material attached on the distalsurface of the cylinder in accordance with an embodiment of theinvention;

FIG. 13(J) is an expanded side view of an FTSC device with a cylinderextending from the distal surface of a cone shaped disc and thecollection material attached on the distal surface of the cone shapeddisc and collection material attached to the distal surface of thecylinder in accordance with an embodiment of the invention;

FIG. 14 is a schematic of an expanded side view of (A) 2 mm Velcro® and(B) 3.1 mm Kylon® material;

FIG. 15(A) is an exploded schematic front view FIG. 12(D) of anendo-cervical FTSC device showing a railing or dam around thecircumference of the hybrid diamond-pear shaped facet in accordance withan embodiment of the invention;

FIG. 15(B) shows a cross section of the endo-cervical FTSC device with arailing or dam wherein the hybrid diamond-pear shaped facet is flat;

FIG. 15(C) shows a cross section of the endo-cervical FTSC device with arailing or dam wherein the hybrid diamond-pear shaped facet is convex;and

FIG. 15(D) shows a cross section of the endo-cervical FTSC device with arailing or dam wherein the hybrid diamond-pear shaped facet is concave.

DETAILED DESCRIPTION OF THE INVENTION

Definitions

The transitional term “comprising” is synonymous with “including,”“containing,” or “characterized by,” is inclusive or open-ended and doesnot exclude additional, unrecited elements or method steps.

The transitional phrase “consisting of” excludes any element, step, oringredient not specified in the claim, but does not exclude additionalcomponents or steps that are unrelated to the invention such asimpurities ordinarily associated with a composition.

The transitional phrase “consisting essentially of” limits the scope ofa claim to the specified materials or steps and those that do notmaterially affect the basic and novel characteristic(s) of the claimedinvention.

As used herein, the term “abrasive material” refers to “toothbrush”bristle brush design, twisted strands of metal wire, twisted strands ofplastic fibers, steel wool, corrugated plastic, Velcro® and Kylon®. Asused here the term “fenestrated loop” refers to a hooked, “candy-cane”shape formed by severing a loop, wherein a short, hooked end is lessthan approximately 50% of the length of the loop. In some embodiments, afenestrated loop is formed by severing a loop once, leaving a short armadjacent to the fenestrated loop.

A ‘facet’ is a surface that is cut into the head of a biopsy device,where the surface's contour differs from the contour of the head of thebiopsy device. The term ‘facet’ is used in analogy to a facet of a gem,where the gem facet has a surface contour that differs from the othersurface contours of the other facets of the gem. A facet that is cut atan angle of 30 degrees relative to the major axis of the head of thebiopsy device is equivalent to a ‘point’ cut in a gem that can produceone side of an octahedron. A facet that is cut at an angle of 3-9degrees relative to the major axis of the head of the biopsy device canbe thought of as equivalent to one of the 30 odd cuts in a gem's crownto produce a ‘brilliant’. In contrast to the facet of a gem which isflat, the facet cut in the head of a biopsy device can have a concave orconvex surface contour. That is a flat facet of a biopsy device hasneither a positive nor a negative radius of curvature. A convex facet ofa biopsy device has a positive radius of curvature relative to the flatfacet. A concave facet of a biopsy device has a negative radius ofcurvature relative to the flat facet. The curvature of a cylinder or rodwill be referred to as positive in contrast to the negative curvature ofa concave facet cut into the cylinder or rod. The curvature of a convexfacet cut into the cylinder or rod will be referred to as positive.

The maximum overall diameter of a FTSC device with one facet is the sumof the maximum diameter of the head and the length of the abrasivematerial attached to the facet. The overall diameter of a FTSC device ata point on the one facet is the sum of the diameter of the head at thatpoint and the length of the abrasive material attached to the facet.

In the following description, various aspects of the present inventionwill be described. However, it will be apparent to those skilled in theart that the present invention may be practiced with only some or allaspects of the present invention. For purposes of explanation, specificnumbers, materials, and configurations are set forth in order to providea thorough understanding of the present invention. However, it will beapparent to one skilled in the art that the present invention may bepracticed without the specific details. In other instances, well-knownfeatures are omitted or simplified in order not to obscure the presentinvention.

Parts of the description will be presented in data processing terms,such as data, selection, retrieval, generation, and so forth, consistentwith the manner commonly employed by those skilled in the art to conveythe substance of their work to others skilled in the art. As is wellunderstood by those skilled in the art, these quantities (data,selection, retrieval, generation) take the form of electrical, magnetic,or optical signals capable of being stored, transferred, combined, andotherwise manipulated through electrical, optical, and/or biologicalcomponents of a processor and its subsystems.

Various operations will be described as multiple discrete steps in turn,in a manner that is most helpful in understanding the present invention;however, the order of description should not be construed as to implythat these operations are necessarily order dependent.

Various embodiments will be illustrated in terms of exemplary classesand/or objects in an object-oriented programming paradigm. It will beapparent to one skilled in the art that the present invention can bepracticed using any number of different classes/objects, not merelythose included here for illustrative purposes.

Systems and methods in accordance with embodiments of the presentinvention can provide for improved presentation and interaction withdigital content and representations of digital content. Representationas used herein includes, but is not limited to, any visual and/oraudible presentation of digital content. By way of a non-limitingexample, digital images, web pages, digital documents, digital audio,and other suitable content can have corresponding representations oftheir underlying content. Moreover, interfaces such as graphical userinterfaces can have corresponding representations of their underlyingcontent.

The invention is illustrated by way of example and not by way oflimitation in the figures of the accompanying drawings in which likereferences indicate similar elements. It should be noted that referencesto ‘an’ or ‘one’ embodiment in this disclosure are not necessarily tothe same embodiment, and such references mean at least one.

In an embodiment of the present invention, the FTSC head samplingsurface takes on the shape of the site to be sampled. In an analogy to akey designed to fit a lock, where the key can be duplicated by making animpression of the key in clay and then duplicating the shape left in theclay; the FTSC head can be shaped to fit the contour of a particularsampling area. In an embodiment of the invention, the FTSC head isintended to sample from the area of the cervix most at risk for aneoplastic transformation. In an embodiment of the invention, byadjusting the surface of the FTSC head, the FTSC head can sample thetransformation zone. In an embodiment of the invention, by adjusting thesurface of the FTSC head, the FTSC head can sample the exocervix.

In various embodiments of the present invention, the FTSC device and thefabric are made of materials such that the hooks of the fabric can besecured to the base or facet of the device. In an embodiment of thepresent invention, the device and the fabric are made of materials thatallow the fabric to be ultrasonically welded to the device. In anembodiment of the present invention, the device and the loops are madeof the same materials and the loop can be ultrasonically welded to thedevice. For example, nylon loops can be ultrasonically welded to a nylonfacet implanted in the curette. Alternatively, nylon loops can beultrasonically welded to a nylon curette head on the facet. In anotherembodiment of the present invention, the hooks can be extruded throughinjection molding during the process of injection molding the curette.In an alternative embodiment of the present invention, the hooks of thefabric can be attached to the device using an adhesive. For example, anultra violet (UV) light activated adhesive can be used to affix thefabric to the device. A railing can be introduced onto the facet of thedevice and the UV light activated adhesive can be placed within theconfines of the dam made by the railing. FIG. 15(A) shows an explodedschematic front view of the endo-cervical FTSC device shown in FIG.12(D) with a head 1680 and a facet 1692, where a railing surrounds thecircumference of the hybrid diamond-pear shaped facet according to anembodiment of the invention. The dotted line 1662 traces the outline ofthe outer perimeter of the facet 1692, while the continuous line tracesthe inner perimeter of the railing 1664, which defines the dam 1666.FIG. 15(B) shows a cross section (section B-B) of the endo-cervical FTSCdevice with a railing 1664 which acts as a dam, wherein the hybriddiamond-pear shaped facet is flat. In an embodiment of the invention,FIG. 15(B) is a 4:1 scale of the FTSC device and the railing dimensionsare height 1672=0.015 inches, width 1674 (i.e., the distance between thedotted line 1662 and continuous line 1664)=0.012 inches, and the dam1666 breadth at its widest=0.25 inches. FIG. 15(C) shows a cross section(section B-B) of the endo-cervical FTSC device and the outer perimeterof the railing 1662 with a railing which acts as a dam, wherein thefacet is convex. FIG. 15(D) shows a cross section (section B-B) of theendo-cervical FTSC device with a railing (inner perimeter 1664) whichacts as a dam, wherein the facet is concave. In an embodiment of theinvention, the railing allows sufficient adhesive to be retained in thedam so that hooks are bound to the facet. In an unexpected result, usinga railing and adhesive to adhere material in which the hooks hadpreviously been adhered significantly decreased the amount of hooks thatwere shed or broken off from the FTSC head during sampling. In thismanner, the railing and the ability to dam the adhesive so that theadhesive bound individual hooks to the facet increased the amount oftissue retained using the FTSC sampling head.

The fabric pad can then be moved towards the adhesive containing faceton the pad backing allowing the pad to be recessed into the cavitycreated by the marginal glue dam. In an unexpected result, the use ofthe UV light activated adhesive was observed to also stabilize thelateral hooks in the fabric, reducing the risk of the hooks and therebythe particulate matter shedding during clinical use.

A biopsy can resolve the causative agent in many if not all of thelesions that are formed from viral, bacterial, fungal or protozoainfections. In the case of HSV, the sample must include cells, not justfluid from the blister, since the virus is in the skin cells of theblister or ulcer. The sample from a lesion or blister collected duringan acute outbreak can be used to identify the agent based on the growthof the virus or substances related to the virus.

Plex ID™ is a high-throughput system based on polymerase chain reaction(PCR) and mass spectrometry analysis to enable identification ofpathogens within six to eight hours. Plex ID™ can detect andcharacterize a broad range of microorganisms in a given sample,including viruses, bacteria and fungi. Although Plex ID™ is notcurrently intended for use in diagnostic procedures, it is available foruse in unregulated areas such as epidemiologic surveillance, biologicalresearch, environmental testing, and forensic research. Plex ID™ hasbeen shown to detect viral isolates from adenovirus, alphavirus,enterovirus, flavivirus, HSV and human parvovirus B19 with a limit ofdetection ranging from 15 to 125 copies.

Focal Biopsy

In various embodiments of the present invention, a trans-epithelialFrictional Tissue Sampling and Collection (FTSC) device can be used toperform biopsies of lesions suspected of harboring disease. Cliniciansare used to a rotational soft bristle brush to collect endocervicalcytology. This soft bristle brush is rotated, with the soft bristlesremoving superficial cells. When a deeper biopsy is required after anabnormal pap smear or to evaluate the cause of vaginal bleeding,clinicians currently use a sharp edge curette. A sharp edge curette isnot designed to and customarily is not rotated to obtain a biopsy.Instead, it is repeatedly inserted, then withdrawn against the canalbeginning at a reference point., As the cervix is cylindrical with acirclular face, the clinician typically starts at a reference point,usually 12:00 o'clock position, and shift, rotating to all positionsaround the clock, sequentially back and forth rotated as it is pushed inand pulled back. A clinician may use the sharp curette, most commonlythe Kevorkian curette, and scrapes the cervical os surface to accumulatecells. The to and from scraping motion shears epithelium and cells whichlie free in the canal and are later collected, as the curette is notalso designed to collect the majority of tissue harvested. The procedurewith the Kevorkian curette is both painful and can cause trauma to thecervix, as it shaves and detaches the epithelium from the underlyingstroma.

Currently a clinician can choose an exo-cervical FTSC or anendo-cervical FTSC biopsy tool. In an embodiment of the invention, aclinician can choose a hybrid exo-cervical/endo-cervical FTSC screeningbiopsy tool. As shown in FIG. 13(H) in an embodiment of the invention,the clinician fits the cylinder 1335 of the hybridexo-cervical/endo-cervical screening biopsy tool projecting from thelarger disk 1330 into the cervical os canal. As shown in FIG. 13(F) inan embodiment of the invention, the surface of one or both the facet1336 present on the cylinder 1335 and the face 1331 of the disc 1330contact one or both the squamo-columnar junction and the endo-cervicalcolumnar epithelium. In an embodiment of the invention, the disc 1330can have a diameter of approximately 35 mm. In an alternative embodimentof the invention, the disc 1330 can have a diameter of approximately 25mm. In an embodiment of the invention, the cylinder 1335 can have adiameter of approximately 9 mm. In an embodiment of the invention, thecylinder 1335 can have a diameter of approximately 6 mm. In anembodiment of the invention, the cylinder 1335 can have a diameter ofapproximately 3 mm.

In an embodiment of the invention, a lesional biopsy site sampled withthe FTSC device can be no larger than approximately 3 mm in diameter. Inan alternative embodiment of the invention, a lesional biopsy sitesampled by the FTSC device can be no larger than approximately 6 mm indiameter. In another embodiment of the invention, a lesional biopsy sitesampled by the FTSC device can be no larger than approximately 10 mm indiameter. In an embodiment of the invention, a lesional biopsy sitesampled by the FTSC device can be no larger than the diameter of theFTSC device head at a position 4 mm distal from the tip. In analternative embodiment of the invention, a lesional biopsy site sampledby the FTSC device can be no larger than the diameter of the FTSC devicehead at a position 9 mm distal from the tip. In an embodiment of theinvention, a lesional biopsy site sampled by the FTSC device can be nolarger than a focal biopsy.

In an embodiment of the invention, lesions are accessible to an examinerduring routine examination. In an alternative embodiment of theinvention, lesions are not accessible to an examiner during routineexamination. In another embodiment of the invention, access to lesionsrequires surgery. In an embodiment of the invention, the tissue surfaceto be sampled is accessible following entry into a body cavity through anatural orifice, canal, or surgical channel. In an embodiment of theinvention, the tissue surface to be sampled is accessible followingentry into a body cavity via a trochar using an endoscope with a biopsyport for inspection. In another embodiment of the invention, the tissuesurface to be sampled is accessible following entry into a body cavityvia a cannula. In another alternative embodiment of the invention, thetissue surface to be sampled is accessible following entry into a bodycavity via an arthroscope, colonoscope, sigmoidoscope, sinus scope andanoscope.

In an embodiment of the present invention, the FTSC device head remainson the lesion due to the design of the device surface. In an embodimentof the present invention, the FTSC device head remains on the immediatearea of intended biopsy/therapy due to the design of the device surface.In an embodiment of the present invention, the FTSC head has a facetwith a fabric for functionally abrading epithelial surfaces including abacking material and a plurality of fenestrated loops attached to thebacking material adhered to the facet. In an embodiment of the presentinvention, the FTSC head facet has a flat surface. In an alternativeembodiment of the present invention, the FTSC head facet has a concavesurface. In another alternative embodiment of the present invention, theFTSC head has a facet with a convex surface. The concave facet headallows a handle attached to the head to be rotated and ensures that thehead remains on the desired location for convex tissue surfaces. Theconvex facet head allows a handle attached to the head to be rotated andensures that the head remains on the desired location for concave tissuesurfaces. The flat facet head with an adhered abrasive fabric allows thehand to be rotated and pressed completley without allowing gaps betweenthe abrasion material and the surface tissue to be sampled whencollecting a biopsy. In an embodiment of the invention, the head of theFTSC device is conical and pointed. In an embodiment of the invention,the head of the FTSC device is elliptical and pointed. In an embodimentof the invention, the head of the FTSC device is multifaceted andpointed.

An unexpected result that was observed during clinical trials of anumber of FTSC devices, undertaken to test various prototype geometries,was that a pointed-tip rod enabled the clinician to more easily dilatethe cervix, while not increasing the risk of damage to the cervixthrough an incision. In an embodiment of the invention, the diameter ofthe head of the FTSC device is a maximum of approximately 8 mm andtapers to a tip of less than approximately 1 mm. In an embodiment of theinvention, the diameter of the head of the FTSC device is a maximum ofapproximately 5 mm and tapers to a tip of less than approximately 1 mm.In an embodiment of the invention, the diameter of the head of the FTSCdevice is a maximum of approximately 4 mm and tapers to a tip of lessthan approximately 0.8 mm. In an embodiment of the invention, thediameter of the head of the FTSC device is a maximum of approximately 3mm and tapers to a tip of less than approximately 0.6 mm. In anembodiment of the invention, the diameter of the head of the FTSC deviceis a maximum of less than approximately 3 mm and tapers to a tip of lessthan approximately 0.6 mm.

In clinical testing, the “sharpened pencil” like design with one flatface, was found to be too rounded or thick toward the middle of the padfor entry into the endocervix in some women with smaller canals. Athinner more streamline profile flattens and narrows the diameter as thecircular shape becomes more elliptical or oval, without becoming tooflat or spear-like in nature. A profile that was too flat can enhancethe “cutting” or shearing ability of the tip when it is pushed into theendocervix and a laceration from the edges can result.

An unexpected result observed during clinical trials was that an FTSCdevice with a maximum diameter of less than approximately 8 mm whichtapered to a tip of less than approximately 1 mm enabled the clinicianto insert the FTSC device into almost any cervical canal, and thengently press to insert the FTSC device further into the cervical os. Inmany cases, the insertion also dialated the cervix to allow entry of thedevice deeper into the canal. This is because the FTSC device head is asmooth tapered tip which acts like a dilator. That is because the distalapproximately 10 mm (corresponding to approximately one-half the lengthof the facet) of the FTSC device head is a smooth tapered tip it actslike a dilator. That is because the distal approximately 13 mm(corresponding to approximately two-thirds the length of the facet) ofthe FTSC device head is a smooth tapered tip it acts like a dilator. Itwas unexpected that an FTSC device can be used to both dilate thecervical OS and enter the cervix. It was also unexpected that thethinner pointed FTSC device did not significantly increase the risk ofdamage to the cervix by causing an incision or inadvertant puncture ofcollateral tissue.

In various embodiments of the invention, the pointed thin head of theFTSC device has one or more facet surfaces cut into the pointed tip toincrease the area sampled in a longitudinal direction along the rod mainaxis. In an embodiment of the invention, the major axis of the facetsurface is parallel with the major axis of the rod. In an embodiment ofthe invention, the minor axis of the facet surface is parallel with themajor axis of the rod. In an embodiment of the invention, the one ormore facet surfaces are at the distal end of the rod. In an embodimentof the invention, the widest portion of one or more of the one or morefacet surfaces is at the distal end of the rod. In an alternativeembodiment of the invention, the thinest portion of one or more of theone or more facet surfaces is at the distal end of the rod. In anembodiment of the invention, one or more of the one or more facets havea concave surface. In an embodiment of the invention, one or more of theone or more facets have a convex surface.

In an embodiment of the invention, one or more of the one or more facetsurfaces are diamond shaped. In an embodiment of the invention, one ormore of the one or more facet surfaces are pear shaped. In an embodimentof the invention, one or more of the one or more facet surfaces aretriangle shaped. In an embodiment of the invention, one or more of theone or more facet surfaces are hybrid triangle-pear-shape. In anembodiment of the invention, one or more of the one or more facetsurfaces are hybrid diamond-pear-shape. The hybrid diamond-pear shapedfacet surface with the diamond end distal to the handle enhances thepointed feature of the FTSC head, while the pear shaped end proximal tothe handle increases surface area. Due to the tapered fit of the deviceinto the canal orifice, the canal itself steadies the device as it isrotated, where pressure can be applied maximally to the fabric surfaceduring rotation.

In an embodiment of the invention, the distal surface of the FTSC thinhead has abrasive material attached. In an alternative embodiment of theinvention, abrasive material is associated with the surface of the FTSCpointed thin head. In another embodiment of the invention, one facetsurface of the FTSC pointed thin head has abrasive material adhered tothe surface. In an embodiment of the invention, one or more of the oneor more facet surfaces of the FTSC pointed thin head has abrasivematerial applied. In another alternative embodiment of the invention,two or more facet surfaces of the FTSC pointed thin head have abrasivematerial applied.

In an embodiment of the invention, the length of the facet on the FTSCdevice tip is approximately 19 mm long. In an embodiment of theinvention, one or more of the one or more facet surfaces begins at thetip of the FTSC device head and extends towards the handle. In anembodiment of the invention, the diameter of the FTSC head 4 mm distalfrom the facet tip is approximately 2 mm. In an embodiment of theinvention, the diameter of the head 9 mm distal from the facet tip isapproximately 2.5 mm. In an embodiment of the invention, the diameter ofthe head 12 mm distal from the facet tip is 3 mm.

In an embodiment of the invention, the maximum overall diameter of aFTSC device with one facet is the sum of the maximum diameter of thehead and the length of the abrasive material attached to the facet. Inan embodiment of the invention, the overall diameter of a FTSC device ata point with one facet is the sum of the diameter of the head at thatpoint and the length of the abrasive material attached to the facet.

In an embodiment of the invention, the abrasive material comprises loopsthat have a short hook end, wherein the distance from the top of theloop to the bottom of the hook is less than approximately 50% of thelength of the loop. In an embodiment of the invention, the abrasivematerial comprises loops that are approximately 4 mm in length. In thisembodiment of the invention, the maximum overall diameter of a FTSCdevice with maximum diameter 3 mm and one facet is 7 mm. In anembodiment of the invention, the abrasive material loops areapproximately 3.5 mm in length. In this embodiment of the invention, themaximum overall diameter of a FTSC device with maximum diameter 3 mm andone facet is 6.5 mm.

In a FTSC device with maximum diameter 3 mm and with abrasive materialcomprising loops that are approximately 3 mm in length, if the distal 4mm of the FTSC head is inserted then the FTSC device tip including theabrasive material has a diameter at this point (4 mm distal from thetip) of approximately 5 mm. In an embodiment of the invention, thediameter of the head greatly facilitates access into the cervical os. Inthis embodiment, the cervix needs be dilated less than approximately 5mmin order for the distal 4 mm of the facet of the FTSC device to enterthe cervical cavity. It has been found that some cervical os diametersare 1-2 mm at the entry point. In this embodiment, the cervix needs bedilated less than approximately 3mm in order for the distal 4 mm of thefacet of the FTSC device to enter the cervical cavity at the entry pointwith minimal bending of the abrasive material loops.

In another embodiment of the invention, a FTSC device with maximumdiameter 3 mm and with abrasive material comprising loops that areapproximately 3.5 mm in length, if the distal 4 mm of the FTSC head isinserted then the FTSC device tip including the abrasive material has adiameter at this point (4 mm distal from the tip) of approximately 5.5mm. In this embodiment, the cervix needs be dilated less thanapproximately 3.5 mm in order for the distal 4 mm of the facet of theFTSC device to enter the cervical cavity. While the Kylon® materialhooks deform and bend somewhat and can be squeezed down tightly with avery tight fit, they lose their ability to abrade if the hooks remainperpendicular, rather than parallel to the canal mucosal surface. Thehooks are intentionally designed to be angular and face away from themucosal surface, as not to penetrate or lacerate primarily, but to shearand frictionally abrade with rotational torque.

An unexpected event was noted when in-vitro post-hysterectomy cervicaltissue was sampled with the prior art, Velcro® or similar fabric, andcompared to the result obtained using the Kylon® fabric. Conventionalhooked fabric such as Velcro® which is designed for optimal fastening toanother material provides hooks that are fenestrated too close to thefabric backing not allowing the hook tips sufficient contact to causeabrasion in a biopsy setting. The Kylon® fabric with its longer hooksand more distally cut fenestrations did permit frictional abrasion andtissue buckling and fracture. The Kylon® fabric provided adequate tissuesample for processing, analysis, and diagnosis.

In an embodiment of the invention, once the thin tapered FTSC device isinserted into the cervix, only the distal 4 mm of the facetcorresponding to three to five hooks of the Kylon® material need to beinside the canal to obtain sufficient material for a biopsy requiringfifteen (15) to fifty (50) copies of DNA. In an alternative embodimentof the invention, once the thin tapered FTSC device is inserted into thecervix, only the distal 9 mm of the facet corresponding to ten (10) totwenty (20) hooks need to be inside the canal to obtain material for abiopsy requiring approximately 100-200 copies of DNA. In anotherembodiment of the invention, once the thin tapered FTSC device isinserted into the cervix, only the distal 12 mm of the facetcorresponding to thirty (30) to forty (40) hooks need to be inside thecanal to obtain material for a biopsy requiring approximately 300-500copies of DNA. Unlike conventional curettage, the FTSC head device canbe rotated and the hooks will contact the os canal and frictionallyabrade, circumferentially being pressed against the endocervicalepithelium, while being pressed and rotated. Since the Kylon® materialhas a greater propensity to ‘hold’ the tissue, more tissue is availablefor pathological analysis. This improves the diagnostic probability ofdetermining the causitive agent. Importantly, tissue yield is crucialwhen scanning pre-cancerous lesions.

In an unexpected result, a prototype FTSC cone-shaped device tip with nofacet and a maximum overall diameter of 9 mm (maximum diameter of headwas 3 mm extending to the tip of approximately 1 mm diameter) was foundnot to fit inside a number of stenotic os cavities even after dilationof the cervix. The prototype FTSC cone-shaped device tip was wrappedwith Kylon® material applied 360 degrees around the device. This addedapproximately 6 mm (twice the length of the loops) to the maximumdiameter of the head. The overall diameter at a point 4 mm distal fromthe tip was 8 mm. Similarly, the rectangular Kevorkian curette was foundnot to fit into most stenotic os cavities.

In an embodiment of the invention, the FTSC device head is a round ortrumpet shaped cylinder. The facet can be flat, concave, or covex inshape. This provides one or more concave facet surfaces at the distalend of a disc or disc-like protrusion without a tapered end. The one ormore concave surfaces allow the FTSC device to be placed on a specificlocation on a body surface, such as the exocervix, vagnia, buccalmucosa, anal mucosa, perianal skin, or vulva and rotated without movingoff the desired location. A convex sampling head best conforms to aconcave tissue surface similar to a “lock in key” nature. A concavesampling head best conforms to a convex tissue surface similar to a“lock in key” nature. A flat tissue surface is best sampled by a flatsampling surface, eliminating gaps between the sampling surface and theepithelium. In an embodiment of the invention, the ability of the FTSCdevice to remain on a fixed location can allow improved sampling ofepithelial tissue from the lesion. Because the FTSC device does not moveoff the lesion, it allows increased rotation of the FTSC device, whichin turn ensures a frictional abrading to enable improved sampling. Incontrast, other methods disclosed in prior art do not disclose, teach orsuggest that the position from which the biopsy is sampled is to bevisually located, guided and retained through the choice of the facetsurface contour. The FTSC device captures surface and exfoliated cellsthrough frictional abrading of the target tissue site without affectingthe ability of the fabric hooks, arranged in rows which permit channels,to open and close, capturing and retaining tissue into those channelsand the fabric body.

FIG. 9 shows a flowchart showing the use of the endo cervical FTSCdevice used to take a tissue sample from within the cervix in accordancewith an embodiment of the invention. Initially a clinician selects anappropriate endo cervical FTSC head for device 900. The cliniciantouches the side of the FTSC head against the cervical opening 910.After the cervix opens, the FTSC head is inserted into the opening 920.The FTSC head can then be placed on the exposed lesion 930. The FTSChead can then be rotated 940. The clinician monitors the FTSC head 950to determine when rotating the FTSC head has sufficently frictionallyabraded the lesion 960. The clinician then removes the FTSC head fromthe cervix 970. The tissue can then be removed from the FTSC head 980.

FIG. 11(A) is a schematic side view of an endo cervical FTSC device 1150showing the handle 1160 with an etched groove 1170 allowing fordetachment, the head 1180 which has a single facet to which is adheredabrasion material 1190. The endo cervical FTSC device 1150 can be storedin a hematically sealed packet (not shown). FIG. 11(B) is an expandedside/frontal view of an endo cervical FTSC head showing the handle 1160which has an etched groove 1170 allowing for the detachment of the head1180, where the head 1180 has a single facet to which is adheredabrasion material 1190, in accordance with an embodiment of theinvention.

Regional Biopsy

In various embodiments of the invention, the FTSC device can be used tobiopsy and screen large geographic areas of tissue at risk for disease.In an embodiment of the invention, the FTSC device can be used to biopsyand screen neoplastic transformation such as, but not limited to, thesquamo-columnar junction of the female cervix in the presence or absenceof visualized lesions. In an embodiment of the invention, the FTSCdevice by providing one or more concave surfaces on an otherwise conicalor rod-like protrusion, allows the device to be placed on a specificlocation and rotated without moving off the desired location. In anembodiment of the invention, the ability to remain on a fixed locationcan provide samples of epithelial tissue from specific locations foranalysis. In this manner, the overall surface can be randomly sampledwith a finite number of biopsy samples. In contrast, other methodsdisclosed in prior art do not allow the position from which the biopsyis to be sampled to be localized. The intent is to frictionally removetissue from a variety of localized positions based on visual evidence ofthe larger area, or knowledge of the “at-risk” landmark area wheredisease is likely to evolve or be harbored, such as the “transformationzone” of the cervix, which can range from approximately 10-40 mm indiameter.

Simultaneous Biopsy of Epithelial Surfaces and Canal-Like Structures

In an embodiment of the invention, the surface of the head has abrasivematerial applied. In alternative embodiments, the device has a head withmaterial applied that contains a central core of fenestrated loops thatare longer (e.g., approximately 4-7 mm long), surrounded by a wider rimof shorter fenestrated loops (e.g., approximately 3 mm in length). Thelonger loops are geometrically suited to insinuate within a centralcanal structure, such as the endocervical canal of the cervix. There issimultaneously uniform contact of the fenestrated loop fiberscircumferentially around the endocervical canal on the flat exocervicalsurface. With rotation and agitation in a back-and-forth motion using abrush, tissue can be used to harvest within the fenestrated loopchannels. In an embodiment of the invention, the abrasive material canbe the Kylon® material fabric. Because the tissue is held by the Kylon®material fabric, when the FTSC head is sent to the pathologist, thepathologist can require a tool to remove the tissue from the FTSC head.Unlike bristle brushes that are twisted, Kylon® material fabric hooksare arranged in rows. In contrast to Velcro® material, the hooks areshallow, and the fenstrations distal and narrow, thus the Kylon® can becombed, and the tissue collected in the biopsy can be combed out. In anembodiment of the invention, a miniature mustache comb can be used toremove the tissue from the Kylon® material fabric. The technician has tocomb the tissue directly out from the Kylon® material fabric into thevial of liquid fixative. Then the vial of fixative containing the mixedtissue can be trapped on a filter paper. Alternatively, in an embodimentof the invention, the tissue can be teased free from the hooks of theKylon® material fabric using a scalpel or tweezers. In an embodiment ofthe invention, the hooks of the Kylon® material fabric can be cut orsheared to remove the tissue from the fabric base for the biopsy. In anembodiment of the invention, the abrasive material can be dissolved inan appropriate solvent to remove the tissue from the abrasive materialfor the biopsy. In an embodiment of the invention, the tissue can berinsed forcefully from the abrasive material on to the filter paper orcollection vessel.

In an alternative embodiment of the invention, approximately 9 mm longcentral fibers are surrounded by approximately 3 mm fibers. In anembodiment of the invention, the device can be inserted into the cervixand rotated with spinning revolutions. Following frictionaltrans-epithelial tissue disruption, the head containing biopsy samplecan be detached and inserted into a liquid vial of fixative.

FIG. 10 is a schematic side view of an exo cervical FTSC device 1000showing the handle 1060 which has an etched groove 1020 allowing for thedetachment of the head 1030, where the head 1030 which has abrasionmaterial 1040 is adhered.

FIGS. 12(A-D) are schematic views of endo- and exo-cervical FTSCdevices, with ribbed handles and tapered waists. In FIGS. 12(A) and (B),the side view and front view of the endo-cervical device 1200 shows aribbed handle 1211 and tapered waist 1213 which are designed to allowthe clinician to easily and rapidly rotate the device 1200. The etchedgroove 1220 allowing for the detachment of the head 1230, is also shown.In FIGS. 12(C) and (D), the side view and front view of the exo-cervicaldevice 1250 includes a ribbed handle 121 and tapered waist 12162 whichare designed to allow the clinician to easily and rapidly rotate thedevice 1250. The etched groove 1270 allowing for the detachment of thehead 1280, and the single hybrid diamond-pear shaped facet 1292 are alsoshown

In an alternative embodiment of the invention, the FTSC device 1300 asshown in FIGS. 13A, 13B, 13F and 13H include a cylinder 1335 with adiameter of approximately 3 mm mounted on a disc 1330 with a diameter of1.5 cm, which is connected to a handle 1310. In FIGS. 13A and 13H thedisc 1330 is connected to the handle 1310 via a handle extension 1312with a weakened portion 1320 to allow detaching of the disc 1330 fromthe handle 1310. In another alternative embodiment of the invention, acylinder 1335 with a diameter of approximately 6 mm is mounted on a disc1330 with a diameter of 3 cm, which is connected to a handle 1310. InFIG. 13A the disc 1330 is cylindrical, while in FIG. 13H the disc 1330is cone shaped and the cylinder 1335 extending from the disc 1330 has afacet. FIGS. 13B and 13F show the face 1336 of the cylinder 1335, whileFIG. 13A shows the cylinder 1335 is covered with abrasive fibers 1340.In Figure FIG. 13B the face is perpendicular to the main axis of thehandle, while in FIG. 13F the face is at an acute angle to the main axisof the handle. In an embodiment of the invention, the face of thecylinder is covered with 3 mm long hooked Kylon® fibers. In anembodiment of the invention, the device can be inserted into the cervixand rotated with spinning revolutions. Following frictionaltrans-epithelial tissue disruption, the head containing biopsy samplecan be detached and inserted into a liquid vial of fixative.

In alternative embodiment of the invention, as shown in FIGS. 13C and13J, a cylinder 1335 or round faced trumpet designed tip with a diameterof approximately 3 mm is mounted on a disc 1330 with a diameter of 1.5cm. In another embodiment of the invention, a cylinder 1335 with adiameter of approximately 6 mm is mounted on a disc 1330 with a diameterof 3 cm. FIG. 13D shows the face 1336 of the cylinder 1335 and the face1331 of the disc 1330. FIG. 13G shows a rounded end 1336 of the cylinder1335 and the face 1331 of the disc 1330. As shown in FIGS. 13C and 13Jthe face 1336 of the cylinder 1335 is covered with abrasive fibers 1337and the face 1331 of the disc 1330 is also covered with abrasive fibers1332. In FIG. 13C the disc is circular, while in FIG. 13J the disc istrapezoid. In an embodiment of the invention, the face of the cylinderis covered with 3 mm long hooked Kylon® fibers and the face of the discis also covered with 3 mm long Kylon® fibers. In another alternativeembodiment of the invention, as shown in FIGS. 13E, the surface of thecylinder 1335 is covered with abrasive fibers 1337 and the face 1331 ofthe disc 1330 is also covered with abrasive fibers 1332. In anembodiment of the invention, the surface of the cylinder is covered with3 mm long Kylon® fibers and the face of the disc is also covered with 3mm long Kylon® fibers.

The clinician inserts the cylinder 1335 onto the exo-cervical tissue orlesion, and position the FTSC device disk surface 1331 flush with theexo-cervix. In an embodiment of the invention the cylinder surface 1336can be flat. In an embodiment of the invention the cylinder surface 1336can be concave. In this embodiment, a slight concave shape can be usedto match the convex cervical contour. In an embodiment of the inventionthe cylinder surface 1336 can be convex. In this embodiment, a slightconvex shape can be used to enhance fit into epithelial concave shapedareas. In an embodiment of the invention the disk surface 1331 can beflat. In an embodiment of the invention the disk surface 1331 can beconcave. In an embodiment of the invention the disk surface 1331 can beconvex. In an embodiment of the invention the disk surface 1331 can beat an inclined angle relative to the cylinder surface 1336. In anembodiment of the invention the disk surface 1331 can be inclined at anangle of 15° relative to the cylinder surface 1336. In an alternativeembodiment of the invention the disk surface 1331 can be inclined at anangle of 30° relative to the cylinder surface 1336. In anotheralternative embodiment of the invention the disk surface 1331 can beinclined at an angle of 45° relative to the cylinder surface 1336. Inanother embodiment of the invention the disk surface 1331 can beinclined at an angle of 60° relative to the cylinder surface 1336. Oncethe cylinder 1336 is inserted and the disk surface 1331 is in contactwith cervical tissue surface, it is pressed and rotated severalrevolutions clockwise and counterclockwise to obtain the biopsy sample.In this embodiment of the invention, the disk surface 1331 of the FTSCdevice is large enough to cover the entire “at risk” area of the cervix,commonly known as the “transformation zone” where cancer precursors andcancer is likely to develop/start. A concave cylinder surface 1336 cansimultaneous dilate the cervix while the concave cylinder design ensuresbetter contact with tissue.

FIG. 14 shows a line drawing representative of a comparison of (A) 2 mmVelcro and (B) 3.1 mm Kylon material. The material 1400 shown in FIG.14(A) has an arc 1410 which is more than approximately 25% of the lengthof the loop 1420 and a relatively narrow fenestration 1430 which is lessthan approximately 0.4 mm. The material 1450 shown in FIG. 14(B) has anarrow arc 1460 which is less than approximately 15% of the length ofthe loop 1470 and a relatively wide fenestration 1480 which is more thanapproximately 0.6 mm.

Frictional Tissue Sampling and Collection Biopsy Devices

In an embodiment of the invention, the frictional tissue sampling andcollection biopsy devices disclosed herein utilize Kylon® material, afabric that includes minute plastic (e.g., nylon) fiber loops that arefenestrated at a minimal distance from the apex of the loop. The loopsflex but do not fracture under minimal to moderate force, or separateunder pressure.

The semi-rigid loops can be pressed in a rotational manner (e.g., insweeping or circular motion) away from or toward the clinician,perpendicular, or at an angle into epithelial tissue surfaces. Thesemi-rigid loops remain flexible enough to cause separation of thefenestrated ends, creating frictional forces sufficient to cause localheating and buckling of the epithelial surface away from the underlyingstroma. The loops are fenestrated such that with applied pressure theyare flexible enough to open and provide access to a “collection well”for histological fragments. The tips of the fiber hooks are orientedaway from the tissue. On pressing and rotation across the tissuesurface, the fibers scrape, buckle and shear the epithelium from theunderlying stroma. The fragments are excoriated from the tissue surfacethrough the concomitant application of frictional forces applied to thetissue surfaces by the fenestrated loops. The frictional forces overcomethe adhesive and binding forces of the tissue below to release fragmentsof various shapes and size, all eligible for collection in a histologylab, and subsequent processing and analysis.

The semi-rigid loops (e.g., made of nylon) hold the tissue fragmentsafter excoriation because the loops are elastic enough to sufficientlyre-close and capture the removed tissue. In addition, the spaces betweenthe fibers also retain excoriated tissue. The frictional forces exceedthe binding forces afforded by adhesion molecules which anchor epitheliato the basement membrane, as well as disrupting Van der Waals forces.

Once the epithelium is frictionally sheared from the underlying stroma,the tissue clumps and epithelial fragments are swept and excavated bythe distal most curved apex of the loop and entrapped within thegeometrically suited spaces between the closed, fenestrated loops.

Thus, the method is frictional abrasion, excavation via rotation andother directional motion, and tissue collection within inter-loopchannels.

The Kylon® material fabric can be cut into uniform shapes such as ahybrid diamond-pear shape, a pear shape, a circular disc or straightedge shape(s) and with uniform height, allowing the device to provide360-degree coverage of tissue surfaces over suspected lesions, without agap within the circumference of the device. The Kylon® base material isalso flexible to allow the material to be applied to a concave or covexsurface. This is in distinction to bristle brushes which are spiral orbent in shape, which present surface gaps. This does not allow uniformcontact with the target tissue, and gaps and spiral or irregularorientation to tissue, that when pressed, agitated, or rotated penetratethe tissue surface causing a traction point, which can cause migrationof the device from the lesion site toward the direction of rotation whensuch devices are pressed onto lesions and rotated or moved for tissueharvesting.

Following biopsy, the head of the device is readily severed from thehandle to allow the head to be deposited in a liquid fixative agent. Inan embodiment of the invention, the handle material is scored (thusweakened) near the head to allow the head to be broken off from thehandle and deposited in liquid fixative, which is usually formaldehydeor alcohol. The Kylon® material fabric, fibers, and/or device head (allwith the tissue entrapped between the fibers) are removed from the vialof liquid fixative to remove the tissue from the head of the device andprocess it for analysis. Therefore, one may intentionally design thedevice in an embodiment in which the user can easily decouple the devicehead from the device shaft. For example, some embodiments can have theshaft inserted into the head via a clip or screw thread mechanism, akey-in-lock design with a pressure release button, or a luer-lock typeof attachment. Once the biopsy is obtained, the head and handle/shaftparts can be decoupled, wherein the handle can be discarded, orsterilized and re-used, and the head immersed in a vial of fixative.

Some methods for removal of tissue from the fiber assembly include usinga brush, rinsing under pressure, immersion and agitation manually ormechanically, or by sonication. Alternatively, the fibers can be shearedfrom the fabric on telfa or other filter paper, and the fibers pluckedoff the paper leaving the entire biopsy specimen. Alternatively, aftertissue is collected into the device channels, tissue can be depositedvia rotation or agitation in a vial of liquid fixative, rinsed off thedevice under pressurized spraying, or removed from the nylon fibers bycutting away the nylon fibers from the fabric (e.g., onto filter paper),thus leaving the tissue on the paper, which can be immersed in fixative.

In preferred embodiments, the Kylon® material fabric fibers aremanufactured in a similar manner to Velcro® or other hook and pile typefastener, where strands are longer than conventional hook and pile,approximately 3 mm in length, can range between 3 mm and 9 mm in length,are fenestrated closer to the apex of the loop instead of close to thebase of one arm of the loop, and thus appear V-wishbone shaped. Theyhave a short hook end with the curvature starting at 2 mm from the base.Because the loop strands are longer, they flex and bend to a greaterangle and twist with greater elasticity when rotated or agitated whencompared with standard Velcro®. Because the fenestration is closer tothe base in standard Velcro®, the loop fenestrations do not separate,leaving the curved smooth surface of the loop in contact with thetissue, and therefore not providing sufficient frictional forces duringrotation to shear and separate the epithelium from the underlyingbasement membrane and stroma.

Preferred embodiments utilize minute plastic fenestrated loops that arepressed perpendicular or at an angle into epithelial tissue surfaceswhich, upon rotational or agitational pressure forces, cause tissueepithelial fragments to be frictionally separated from the underlyingtissue basement membrane and stroma. The channels between thefenestrated loops entrap and collect the tissue fragments. The processis similar to curettage with a blunt curved tool, which also scrapes,shears and strips epithelium from the underlying stroma of targettissues. On the other hand, the process is in contrast to sharpcurettage where the purposefully sharp edge of the curette firstincises, pierces, then shaves and scoops epithelium and underlyingstroma from the tissue surface. The process described herein is lessperceptible to patients than conventional biopsies and causes a smalleramount of blood loss and trauma.

In an embodiment, the present invention relates to a frictionaltrans-epithelial tissue apparatus. In various embodiments, the apparatuscomprises approximately 3 mm or smaller loops adherent to and projectingperpendicular from a surface, with a density of approximately 50-1000loops per square inch, evenly spaced or arranged in rows. The loops canbe intact or fenestrated at the center or at their lateral aspect toallow for added flexibility and constructed from plastic, metal, oranother stiff material. The rounded end of the loop is opposite thesurface.

Loops can be of sufficient flexibility to withstand frictional forcesand not fracture, and of sufficient tensile strength to generatesufficient frictional shear force during a sweeping or circular motionof the device to remove epithelium from tissue. The space between loopscan serve to capture and harbor the sampled tissue.

In various embodiments designed for focal lesional biopsy, a flat,flexible surface, which anchors the loops, can be approximately 10-15mm, but is most practically approximately 5-10 mm in diameter andcircular in shape. In alternative embodiments of the present invention,a concave surface anchors the Kylon® material loops. The shape can beanother geometrical design if it affords an advantage in covering thetarget tissue area for sampling. The head can be hinged in such a waythat it can be folded or compressed, inserted through a small endoscopicchannel, and then reinstated to its original state with a samplingsurface. It can be comprised of plastic, cloth, or another compositematerial. The loops can be threaded through and project away from thehead towards the tissue surface. In various embodiments of the presentinvention, a hub fiber or “pin” that penetrates and anchors the centerof the disc on the target biopsy area, can serve as a central post torotate the disc around for stability.

In other embodiments intended to screen larger, regional tissue sites atrisk for neoplastic transformation or other disease process, the shapecan be circular, where the diameter can range from approximately 10-50mm, and the loops can project at varied distances from the head towardsthe tissue surface. For the purpose of histological screening to detectcervical neoplasia, the central approximately 5 mm diameter discprojects longer (approximately 5-25 mm) fenestrated loop fibers, and canbe surrounded circumferentially by the aforementioned approximately 3-23mm long loop fibers. The longer fibers can insinuate inside canalstructures, (e.g., the endocervical canal) simultaneously with contactof the shorter fibers with an outer endothelial surface (e.g., theexocervical surface). Upon pressure and rotation or agitation, theendocervical and exocervical tissues can be simultaneously frictionallysheared and collected. Histological screening can be necessary tocorrectly reflect the presence or absence of epithelial pathology,because adhesion molecules can prevent representative exfoliation fromdiseased tissue in some cases, leaving cytological screening methodslacking in accuracy. (see for example Lonky et al., J Low Genit TractDis. (2004) 8:285 “False-negative hybrid capture II results related toaltered adhesion molecule distribution in women with atypical squamouscells pap smear results and tissue-based human papillomavirus-positivehigh-grade cervical intraepithelial neoplasia” and Felix et al., Am JObstet Gynecol. (2002) 186:1308, “Aberrant expression of E-cadherin incervical intraepithelial neoplasia correlates with a false-negativePapanicolaou smear”).

Preferably, a frictional trans-epithelial biopsy sample is taken from alesion or an anatomical region that is predisposed to disease.

In various embodiments of the present invention, the device includes aplastic, metal, or mixed composition disk or curved convex head, whichprovides a flat surface for a cylinder to be attached. The disk can beequal or greater in diameter than the cylinder. The disk isapproximately 5-10 mm in length while the flat, concave or convexcylinder is less than approximately 3 mm in thickness.

In various embodiments of the present invention, the applicator probecan be comprised of a rod or cylindrical shape including any suitablematerial (e.g., wood, glass, plastic, paper or metal), which has thebase, surface and loop unit at its most distal end, wherein theapplicator probe is approximately 2-5 mm in diameter and approximately15-30 cm in length. It is constructed larger or smaller depending on theaccess to the tissue surface. The shaft of the rod or cylindrical shapedapplicator probe can be rigid or semi-rigid so as to not bow or arc whenpressure is transmitted from the handle to the device head.

A handle into which the applicator probe can be transfixed is optionallymechanical, providing motorized rotational, drill-like movement oragitating vibration.

The device handle can be composed of stiff material, preferably plasticsimilar to Lucite, clear or opaque in coloration, rigid nylon plastic,or alternatively can be glass, wood or metal. The device head can take avariety of shapes, cylindrical or tapered in design, but the distal mostsurface face is circular, square, or polygonal, and can be composed ofplastic (e.g., nylon). The device head diameter can range fromapproximately 5-50 mm. The abrasive material fabric can be welded to thenylon surface ultrasonically, or can alternatively be attached viaadhesive, or via a rim or collar (e.g., which snaps on to the surfaceinto a recess in the head of the device).

In some embodiments, the clinician examines tissue surfaces and choosesan area to be sampled based on the presence of a suspicious lesion. Inother embodiments, the clinician chooses an anatomical landmark known tobe “at risk” for neoplastic or disease transformation for the purposesof sampling the entire chosen surface. The new learning is that a deepertrans-epithlial biopsy grade sample can be obtained with a minimallyinvasive approach with minor discomfort or trauma. Thus far, in 15 casesin a prospective clinical trial, patients report the biopsy procedureusing Kylon® biopsy material on the described applicator(s) induceslittle or no discomfort, with minor bleeding graded less thanconventional curette or sharp biopsy devices.

The handle or applicator probe is grasped at its proximal end or handle.The distal portion or head of the device contains the base, surface andloops that project perpendicular from the base towards the tissuesurface with the more rounded ends that are pressed against the tissuesurface.

With moderate pressure, the examiner simultaneously presses and rotatesthe device against the tissue several times in a clockwise orcounterclockwise direction, or agiating motion in alternating 75-120degree ratations, clockwise and counter clockwise. These actions causean opening or separating the fenestrated loops, thus performingfrictional disruption of the tissue surface. Alternatively, a sweepingmotion can be used. If a motorized handle is used, it can be activatedto assist in the rotation or vibration of the device.

The harvested tissue is collected from the tissue surface, and sometissue already trapped in the loops themselves can be inspected and canbe teased from the loops, or the loops transected from the fabric andseparated, and the remaining tissue placed in a fixative solution.

As shown in FIG. 1, fabric with fenestrated loops (1) is connected toplatform (2), which is in communication with head (3), located at adistal end of handle (5), optionally including an elongated rod (4).Referring to FIG. 3A, moderate force (8) is applied against a tissuesurface (7). The device head is rotated (9) on the surface tofrictionally separate or agitate the surface epithelium. The device headis rinsed or placed with tissue in the loops into fixative forsubsequent pathological analysis.

An apparatus with a conical platform is depicted in FIG. 2. In FIG. 2A,fabric with fenestrated loops (1) is connected to conical platform (6).Referring to FIG. 3B, an apparatus with a conical platform can beinserted into a canal or cavity. The device head is rotated (9) whilemaintaining pressure force in direction (8). The device head with tissuein the loops is rinsed, combed or teased free , or placed intopathological fixative.

An apparatus with a motor configured to rotate the platform is depictedin FIG. 4. Fabric with fenestrated loops (1) is attached to platform (2)on head (3) at the distal end of an elongated rod (4), which is attachedto a motorized handle (5).

In some embodiments, the head is detachable from the elongatedrod/handle. Referring to FIG. 5, a detachable head configuration allowsthe distal portion with head (3), platform (2), together with attachedfabric containing loops, to be detached and placed into a preservativemedium for later tissue removal and pathological processing. Someembodiments can have the shaft inserted into the head via a clip orscrew thread mechanism, or a luer-lock type of attachment (23). Tissuefragments that remain attached to the detachable head are in addition toany free tissue obtained and collected from the tissue surface or thedevice as a result of the frictional tissue sampling.

Referring to FIG. 6, epithelial tissue samples are obtained byfrictional transepithelial tissue disruption. A representation of tissuewith a squamous epithelial lined surface is depicted in panel (A). Thesquamous epithelial multilayer (11) is shown with superficial flat andbasal cuboidal epithelium. Basement membrane (12) separates the squamousepithelial multilayer from the subcutaneous tissue stroma (13) and theunderlying sub-stromal tissue (14). FIG. 6B depicts application of thefrictional biopsy device to the tissue surface. The device head (3) isapplied (24) to a chosen area where curved portions of the fenestratedloops (1) press against the epithelial surface. A representation of twoabutting hooks is shown, creating a collection channel. A shorter arm(15), adjacent to the fenestrated loop (1), can remain followingsevering of an initial continuous loop to create the fenestrated loop.In FIG. 6C, simultaneous pressure, agitational, and rotational force(16) splays and separates the hooks/loops. Frictional abrasive forcescreate heat which buckles the epithelial surface. Referring to FIG. 6D,sufficient abrasion creates shearing and fracture of the epithelialsurface at varying depths which can include fracture through thebasement membrane into the subcutaneous layer. As shown in FIG. 6E, thehooks insinuate into the fracture plane, and with additional abrasiveforces continue to shear the tissue fragments, while simultaneouslyretaining the tissue for capture and collection. At the completion ofthe biopsy process (FIG. 6F), the collection of hooks arranged in rowscreates channels that collect and sequester the tissue and cell clusterfragments within the channels. When the device is removed from theepithelial surface, additional sample collection is achieved due to theflexibility and recoil of the hooks.

Referring to FIG. 7A, frictional trans-epithelial tissue disruption witha focal biopsy apparatus is shown at the outer lip of the exocervix(17), alternatively known as the “transformation zone” of the cervix(18). In this configuration, fenestrated loops (1) approximately 3 mm inlength are used to disrupt and collect tissue fragments. FIG. 7B depictsan enlarged focal biopsy apparatus, with an enlarged view of fenestratedloops (1) attached to platform (2).

Referring to FIG. 8A, simultaneous trans-epithelial biopsy of epithelialsurfaces and canal-like surfaces, in particular, biopsy of theendocervical canal (20) and the exocervical area around the endocervicalcanal (i.e., the transformation zone), is shown (19). Referring to FIG.8B, a central core of elongated loops of approximately 5-25 mm in length(21) are surrounded by a wider rim of shorter fenestrated loops ofapproximately 3-23 mm in length (22).

The frictional tissue sampling and collection device can be used on anybody surface, both external to the body, body cavities, or on internalorgans. To access epithelial surfaces of internal body organs, thedevice head can be deflated, folded or collapsed to pass through a smallaperture or port, and re-opened or expanded to fully expose the fabricto the biopsy surface. This device can be used on humans or any otherliving organism with an epithelial surface. Any tissue surface can besampled. The ease of use in each case will be related to the strength ofthe individual tissue adhesion and binding forces in specific locations.The loops themselves can harvest the tissue and also serve as tissuecollection reservoirs for later storage once placed in a fixativemedium. The platform with the loops can be detached from any applicatorfor later examination and processing (i.e., decoupled from theinstrument used to press against tissue surfaces to obtain the tissuesample).

If the tissue surface is a canal or concave shaped area of the body,instead of a perpendicular platform design, the loops are directlyattached to the probe itself, which is gradually tapered at the end tofacilitate insertion into the canal. The loops project perpendicularlyfrom the probe surface at its distal end, and the unit, once placed intothe canal that is lined on its surface with epithelium, contacts suchepithelium snugly.

The loops can be mounted on the platform or project from the rim surfaceof the platform, perpendicular or at an angle to the platform along themargin of the platform, or attached to other delivery applicators,including the examiner's gloved finger, or other surgical instruments.The platform can be any shape or size which can fit on a tissue surface.The base assembly can be any shape or size, and can be permanently rigidor collapsible.

If the tissue surface lies within a canal-shaped tissue surface, theloops can be attached directly to the applicator probe, which can beinserted into the canal-shaped body cavity. The probe with the loopsprojecting from the surface and contacting the epithelium is rotated,causing the frictional disruption sampling from the tissue surface. Theshape of the probe can be constructed in any shape that allows a snugfit into the canal. The loops can be arranged in rows or equally spaced,allowing for maximal contact and tissue collection.

Some embodiments of the invention comprise a motorized mechanicalassistance via a mechanical handle into which the most proximal end ofthe applicator probe is inserted. Such mechanical assistance can enhancethe rotational or vibratory force that the device transmits to thetissue after contact is established. This can increase the frictionalforces and the speed of the tissue disruption/sampling and shorten theprocedure time.

Preferred Parameters of Fibers

The frictional sampling loops of the invention are collectively referredto as fenestrated loop fibers. In particularly preferred embodiments,the fibers are made using the hooked side of a modified Velcro® or otherhook and pile type fastener, where the strands are approximately 3 mm inlength and are V-wishbone shaped. They have a short hook end with thecurvature starting at approximately 2 mm from the base. In variousembodiments, the loops can be approximately 2.5-25 mm in length,approximately 3-5 mm in length, approximately 3-10 mm in length,approximately 3-15 mm in length, approximately 3-20 mm in length orapproximately 3-25 mm in length.

In comparison, standard Velcro® is approximately 2 mm long and is morehooked. Thus, the loops of the present invention are longer than thoseof standard Velcro®, they are made of a similar nylon material comparedwith standard Velcro®, are more flexible when rubbed on a tissue surfacedue to their length, and they have shorter loops that hook nearer to theend of the strands. In particular, the distance from the top of the loopto the bottom of the hook is preferably less than 50% of the length ofthe loop, more preferably less than 40%, still more preferably less than30%, and even more preferably less than 20% the length of the loop. Thisdistance is also preferably at least 1% the length of the loop, morepreferably at least 5% the length of the loop, and still more preferablyat least 10% the length of the loop. A case series of threepost-hysterectomy samples proved that conventional hooked fabric such asVelcro® mounted on sampling devices, pressed and rotated on the cervicalepithelial surface were incapable of harvesting tissue for biopsy, whilethe re-engineered Kylon® fabric frictionally abraded tissue to atrans-epithelial depth.

Thus, the invention includes hooks in all of the ranges between any ofthe preferred minimum distances and any of the preferred maximumdistances. The bottoms of the hooks are preferably arranged so that theyare all approximately the same distance from the loop, although this isnot strictly necessary. Because the hooks are cut at a relatively distallocation, the ends of the hooks are more accessible to the tissuesurface allowing for uniform transmission of frictional forces to thetissue surface. As a result, the action of the fibers more effectivelybuckle and shear the tissue, while the loops sweep over and capture thetissue.

In a preferred embodiment, the loop fibers are arranged so as toefficiently capture tissue. Thus, in one preferred embodiment, thefibers are arranged in an orderly orientation. For example, the fiberscan be arranged in rows between which the tissue can be captured. Thehooks can be arranged to be oriented at approximately the same angle anddirection in each of the fibers. Thus, the fibers can be organized suchthey all have a consistent direction and angle of orientation. Inaddition, the spacing between each of the fibers can be made to be thesame or different.

In use, the device can be oriented so that the fibers are perpendicularto tissue, and then pressure is applied. As a result, the epithelialsurface is frictionally sheared. Thus, the fibers are preferably mountedon a flat or curved platform, optimally 4-10 mm in diameter so asoptimize this process. However, alternatively shaped platforms can alsobe used in certain embodiments. Because the fibers can be mounteddirectly on the platform, which can be flat or slightly curved, theorientation remains evenly spaced and the spaces inside the fenestratedloops and between them remain evenly distributed to facilitate tissuecapture.

In some embodiments the platform can be in the form of a thumbtack,wherein it is attached to the handle. However, the platform and handlecan take on a variety of forms. It is envisioned that the handle and theplatform can be molded as one piece, and the fibers (e.g., modifiedVelcro® can be attached with adhesive or via ultrasonic or thermalwelding of the fabric to the platform.

In an embodiment of the invention, the abrasive fabric can be attachedor sewed into another fabric or material such as the finger of a glove,with the human finger or hand functioning as the applicator tofrictionally press and abrade the tissue surface.

In an embodiment of the invention, the Kylon® fabric can be applied toexisting surgical instruments such as a body part probe, clamp, ortissue manipulator via an adhesive. In this manner, the surgicalinstrument to which the Kylon® fabric is adapted serves as a biopsycollection device.

In an embodiment of the invention, the abrasive fabric can bederivatized with functional groups to bind specific marker moleculespresent on cells of interest. PCT Application Number: PCT/US2009/053944,titled “Porous Materials for Biological Sample Collection” to Zenhausernet al, which is incorporated by reference in its entirety, describes aninorganic material which can be used as the abrasive material ratherthan for example the Nylon which is used in Velcro® to allow thespecific binding and/or the solubilization of the abrasive material withapproprtiate solvents.

Method of Inducing an Immune Response by Autoinoculation

In some embodiments, the trans-epithelial, frictional tissue samplingand collection devices described herein are utilized to agitate anddisrupt epithelial cells containing a pathogen, or cellular proteinsaltered by a pathogen, to induce an immune response against thepathogen. This results in auto-inoculation of tissues that harborpathogens and macromolecules such as virally altered DNA and/oroncogenic proteins. The method can also be termed therapeutic frictionalabrasion-excoriation. This method is advantageous when a pathogen isnormally able to evade an immune response. For example, some virusesremain in surface epithelial layers where they are sequestered from theimmune system. Other viruses can be integrated into cellular DNA,thereby evading immune detection.

The methods of inducing an immune response against a pathogen thatnormally evades the immune system comprise the steps of (a) disruptingepithelial cells containing the pathogen, virally altered DNA, orcellular oncoproteins with a micro-curettage device described herein,and (b) introducing the pathogen into the bloodstream of a patient toelicit an immune response.

In some embodiments, the trans-epithelial, frictional tissue samplingand collection devices described herein are utilized to disruptepithelial cells to induce an immune response against humanpapillomaviruses (HPVs). HPVs are persistent viruses that can remain intheir hosts for long periods of time before causing any ill effects.Generally, the host reacts to viral pathogens by generating both humoraland cell-mediated responses. Humoral responses are typicallyantibody-mediated and involve the secretion of antibodies such asimmunoglobulin A (IgA) and immunoglobulin G (IgG) by B lymphocytes.Cellmediated responses, on the other hand, are carried out by immuneeffector cells such as dendritic cells (DCs), natural killer (NK) cells,macrophages and T lymphocytes which secrete a number of cytokinesincluding interferon (INF) and tumor necrosis factor (TNF), andup-regulate the expression of Fas ligand (FasL) and TNF-relatedapoptosis inducing ligand (TRAIL) on their cell surface.

In the case of HPV infection, the immune response is frequently weak orundetectable, and accompanied by little or no inflammation. Even when animmune response is elicited, it may not be able to clear the virus.Disruption of the epithelial surface by frictional tissue disruptioninduces repair and inflammation and serves to autoinoculate the patient.Without wishing to be bound by any theory, exposure of the epithelialsurface to frictional tissue disruption, uniquely induced by theapparatus and methods disclosed herein through local heating fromfriction forces exerted, can enhance the induction of repair,inflammation and an immune response following patient autoinoculation.Agitation or scrubbing of a lesion serves to introduce viral particlesinto the bloodstream of a patient, where they can trigger a humoral orantibody-related immune response. In addition, the method can fracturecells releasing antigens locally within the tissue stroma, inducing acell mediated response associated with the release of cytokines andattraction of helper and killer T cells to the sampled tissue area.

Advantageously, the method of the present invention auto-inoculates apatient with viral particles of the specific viral serotype(s) that thepatient is infected with. In contrast, current vaccine strategies areeffective on a subset of HPV strains. For example, GARDASIL® by Merck &Co., Inc. is indicated to help prevent cervical cancer, precancerous andlow-grade cervical lesions, vulvar and vaginal pre-cancers and genitalwarts caused by human papillomavirus (HPV) types 6, 11, 16 and 18, andCervarixT® by GlaxoSmithKline is an HPV 16/18 cervical cancer candidatevaccine. The vaccine is commonly injected in a limb, not the targetorgan at risk, the cervix, and has been only documented to elicit ahumoral antibody immune reaction.

Drug Application

In some embodiments, an adjuvant drug or an immune modulating agent isused in combination with the autoinoculation method, thus augmenting animmune response. For example, Imiquimod (Aldara® topical cream,manufactured and marketed by Graceway Pharmaceutical Company) isapproved for the treatment of actinic keratosis, external genital wartsand superficial basal cell carcinoma (sBCC), a type of skin cancer. Animmune response can be enhanced by using such immune modulating agentsin combination with autoinoculation by the methods described herein. Theadjuvant drug can be applied to the fenestrated loop fibers directlyakin to toothpaste on a toothbrush, or a channel within the applicatorcan be used to transmit the drug from the top of the handle by means ofa squeeze bulb or syringe, through a small lumen in the center of thefabric disc, concomitant with the tissue disruption, delivering druginto the fracture crevices created during the frictional buckling andshearing process created by the device.

Some embodiments comprise a method of drug delivery to a pathologicallesion or areas of tissue that concomitantly disrupts tissue planes,creating crevices or pathways for drugs to enter via intra-epithelialand sub-epithelial spaces. This is in contrast to topical therapies,which are slowly absorbed into and through the epithelia. Intra-lesionalapplication is more focused and requires less drug, presenting less riskof side effects.

Any type of drug (e.g., ablative, antibiotic, antiseptic, immunemodulating, etc.) can be used.

In some embodiments, drug is delivered via an applicator comprising afabric with fenestrated loops as described herein. Drug is applied in amanner akin to applying toothpaste to a toothbrush, or drug can injectedonto the platform or the apparatus via a channel leading through ahollow applicator handle. The drug application apparatus can optionallyhave an element through which the drug is delivered (e.g., a syringewith a locking mechanism). Drug is applied to a “wound” created byfrictionally agitating the tissue. In some embodiments, the fenestratedloops can be impregnated with a drug during manufacture, wherein thedrug leeches out into the disrupted tissue when the fiber contacts andmacerates/disrupts the tissue.

While the present invention has been described in some detail forpurposes of clarity and understanding, one skilled in the art willappreciate that various changes in form and detail can be made withoutdeparting from the true scope of the invention. All figures, tables, andappendices, as well as patents, applications, and publications, referredto above, are hereby incorporated by reference.

In another embodiment of the invention, a Radio Frequency IDentification(RFID) tag is imbedded in one or more of: the head of the FTSC device,the handle of the FTSC device, or a wrist bracelet worn by theclinician. In an embodiment of the invention, the RFID tag is used toidentify the FTSC head device and thereby determine the parameters underwhich the FTSC device was used. In one embodiment of the invention, theRFID tag operates using an Ultra High Frequency (UHF) signal. In anotherembodiment of the invention, the RFID tag operates using a microwavefrequency signal.

In an embodiment of the present invention, a RFID reader is present inthe operating theater which can then read the RFID tags in theindividual FTSC devices. In an embodiment of the invention, the RFIDreader can be positioned so that the RFID tag antenna is least affectedby any conducting material.

In one embodiment, the RFID tag is read-only. In another embodiment, theRFID tag contains an Electrically Erasable Programmable Read-Only Memory(EPROM), which enables both read and write functions. In an embodimentof the invention, the RFID tag is passive. In another embodiment of theinvention, the RFID tag is semi-passive, containing a source of energysuch as a battery to allow the tag to be constantly powered. In afurther embodiment of the invention, the RFID tag is active, containingan internal power source, such as a battery, which is used to power anyIntegrated Circuits (ICs) in the tag and generate the outgoing signal.In another embodiment, the tag has the ability to enable locationsensing through a photo sensor.

In one embodiment of the invention, means of communication with a basestation is embedded in the FTSC device.

In one embodiment of the invention, the communication means utilizes oneor more of a wireless local area network; a wireless wide area network;a cellular network; a satellite network; a Wi-Fi network; and a pagernetwork. In one embodiment of the invention, a modem capable ofcommunicating with one or more of the aforementioned networks isembedded in the FTSC device. In the following discussion the term‘cellular modem’ will be used to describe the device embedded. The term‘cellular modem’ will be herein used to identify any device ofcomparable size capable of communicating over one or more of theaforementioned networks. In one embodiment of the invention, thecellular modem can be a Code Division Multiple Access (CDMA) modem. Inan embodiment of the invention, a RFID reader and associate integratedcircuit processor can be embedded together with the cellular modem inthe FTSC device. In such an embodiment, the RFID tags and RFID readercan be positioned to optimize the RFID read of the RFID tags from theavailable devices.

In an embodiment of the invention, a system for using and monitoring anFTSC device during a surgical procedure, comprises an FTSC head andhandle, a comb for removing the tissue from the FTSC head, and a meansfor rotating the FTSC handle. The means for turning the FTSC head caninclude an automated device. The FTSC rotating device can include aninput module for selecting parameters for use with the FTSC device,wherein the input module selects parameters based at least in part onthe FTSC head device selected, a sensor for monitoring the FTSC headrotating velocity, a processor for comparing the rotational velocity ofthe FTSC head and the selected parameters and automatically adjustingthe FTSC head rotation velocity when the comparison indicates anincreased or decreased head rotation is required. The input module canreceive audio, tactile or visual feedback to adjust the FTSC deviceduring the surgical procedure.

In an embodiment of the invention, the FTSC device can be applied in anysurgical, scientific, crime investigation or veterinary application thatrequires the use of a regulated constant or variable rotating tissuesampler. This can include laboratory equipment that requires tissuesampling, storage or any other clinical procedure.

A method for simultaneously dilating a cervix and obtaining atransformation zone biopsy with minimal discomfort to a patientcomprising selecting a FTSC head with a facet in the FTSC head, whereinthe FTSC head is received in a handle, wherein the FTSC head is selectedto dilate the cervix without causing discomfort to the patient.Inserting the head of the FTSC device into the non-dilated cervix to adepth that does not cause discomfort to the patient. Waiting for thecervix to at least partially dilate. Further inserting the head of theFTSC device into the partially dilated cervix to a depth that does notcause discomfort to the patient. Incrementally repeating these stepsuntil the facet at least partially rests against the transformationzone. Rotating in a first direction one or both the handle and the FTSChead to frictionally abrade the transformation zone. Removing the FTSChead from the cervix. Using a comb to remove tissue from the cervix bybrushing the head in a second direction, wherein the second direction isopposite of the first direction. Depositing the tissue removed fromcombing the head in a fixing solution.

A device for obtaining a biopsy tissue sample comprising a head with aproximal end, a distal end, wherein the head has a first maximumdiameter. Further comprising a facet extending from the distal surfaceof the head, wherein the facet has a surface contour, wherein thesurface contour has a second maximum diameter, wherein the secondmaximum diameter is at least 1 mm less than the first maximum diameter,wherein the perimeter of the facet has a railing, wherein the railingcan be used to form a pool of adhesive prior to the adhesive beingcured. Further comprising a handle with a proximal and a distal end,wherein the proximal end of the head is connected to the distal end ofthe handle. Also comprising an abrasive material, wherein the abrasivematerial is adhered to the facet with the adhesive.

A device for obtaining a biopsy tissue sample comprising a head with aproximal end, a distal end and a handle with a proximal end and a distalend, wherein the proximal end of the head is connected to the distal endof the handle. The device further comprising a facet associated with thedistal surface of the head, wherein the facet has a surface contour,wherein a plurality of loops extend from the surface of the facet,wherein the plurality of loops are secured to the facet, wherein whenthe device is in contact with tissue and rotated the plurality of loopsfrictionally abrade the tissue to obtain a biopsy sample, wherein theplurality of loops are made of the same material as the facet.

The foregoing description of embodiments of the methods, systems, andcomponents of the present invention has been provided for the purposesof illustration and description. It is not intended to be exhaustive orto limit the invention to the precise forms disclosed. Manymodifications and variations will be apparent to one of ordinary skillin the relevant arts. For example, steps performed in the embodiments ofthe invention disclosed can be performed in alternate orders, certainsteps can be omitted, and additional steps can be added. The embodimentswere chosen and described in order to best explain the principles of theinvention and its practical application, thereby enabling others skilledin the art to understand the invention for various embodiments and withvarious modifications that are suited to the particular usedcontemplated. Other embodiments are possible and are covered by theinvention. Such embodiments will be apparent to persons skilled in therelevant art(s) based on the teachings contained herein. The breadth andscope of the present invention should not be limited by any of theabove-described exemplary embodiments, but should be defined only inaccordance with the following claims and their equivalents.

What is claimed is:
 1. A method for simultaneously dilating a cervix andobtaining a biopsy of a transformation zone with minimal discomfort to apatient comprising: (a) providing a frictional tissue sampling andcollection (FTSC) head including a facet with a facet contour in theFTSC head, where the FTSC head is received in a handle, where the FTSChead is provided to dilate the cervix without causing discomfort to thepatient, where the facet includes a plurality of loops; (b) insertingthe FTSC head into the non-dilated cervix to a depth that does not causediscomfort to the patient; (c) waiting for the cervix to at leastpartially dilate; (d) further inserting the FTSC head into the partiallydilated cervix to a depth that does not cause discomfort to the patient;(e) incrementally repeating steps (c) and (d) until the facet at leastpartially rests against the transformation zone; (f) rotating in a firstdirection one or both the handle and the FTSC head to frictionallyabrade the transformation zone with the plurality of loops; and (g)removing the FTSC head from the cervix with the biopsy.
 2. The method ofclaim 1, where one or more of FTSC head size, facet contour, facet shapeand FTSC head shape are selected based on the curvature of the cervix tobe sampled to dilate the cervix without causing discomfort to thepatient.
 3. The method of claim 2, where the facet contour selected isconcave when the cervix has a convex shaped contour.
 4. The method ofclaim 2, where the facet contour selected is convex when the cervix hasa concave shaped contour.
 5. The method of claim 1, where the facet iscut at an angle relative to a main axis of rotation of the FTSC head ofbetween: a lower limit of approximately 2 degrees; and an upper limit ofapproximately 30 degrees.
 6. The method of claim 1, where the facet hasa shape selected from the group consisting of pear-shaped, triangular,diamond and hybrid diamond-pear-shape.
 7. The method of claim 1, wherethe facet has a length between: a lower limit of approximately 4×10⁻³ m;and an upper limit of approximately 3×10⁻² m.
 8. A method forsimultaneously dilating a cervix and obtaining a biopsy of atransformation zone with minimal discomfort to a patient comprising: (a)providing a head including: a first portion with a proximal end, a firstdistal end, a first facet extending from the proximal end to a seconddistal end, where the first facet includes a first plurality of loops, asmooth surface extending from the proximal end to the distal end and afirst main axis of rotation from the proximal end to the distal end; anda second portion with a second facet, where the second facet includes asecond plurality of loops, where the head is received in a handle, wherethe head is selected to dilate the cervix without causing discomfort tothe patient; (b) inserting the head into the non-dilated cervix to adepth that does not cause discomfort to the patient; (c) waiting for thecervix to at least partially dilate; (d) further inserting the head intothe partially dilated cervix to a depth that does not cause discomfortto the patient; (e) incrementally repeating steps (c) and (d) until oneor both the first facet and the second facet at least partially restagainst the transformation zone; (f) rotating in a first direction thehandle to frictionally abrade the transformation zone, with one or boththe first plurality of loops and the second plurality of loops, wherethe smooth surface facilitates rotation of the head with minimal pain tothe patient; and (g) removing the head from the cervix to retrieve thebiopsy.
 9. The method of claim 8, where one or more of the head size,the first facet length, the first facet contour, the first facet shape,the second facet length, the second facet contour, the second facetshape are selected based on the curvature of the cervix to be sampled.10. The method of claim 8, where the first facet is cut at an anglerelative to the first main axis of rotation of between: a lower limit ofapproximately 2 degrees; and an upper limit of approximately 30 degrees.11. The method of claim 8, where the first facet has a shape selectedfrom the group consisting of pear-shaped, triangular, diamond and hybriddiamond-pear-shape.
 12. The method of claim 8, where the first facet hasa length between: a lower limit of approximately 4×10⁻³ m; and an upperlimit of approximately 3×10⁻² m.
 13. The method of claim 8, where thesecond portion has a second main axis of rotation perpendicular to thefirst main axis of rotation.
 14. The method of claim 8, where the secondportion has a second main axis of rotation parallel to the first mainaxis of rotation.